ABSTRACT
Background: OSE2101 (Tedopi) is an anticancer vaccine that increased overall survival (OS) (HR 0.59, p=0.017) versus Standard of Care Chemotherapy in the population of interest (PoI N=118) of patients with IO secondary resistance after sequential CT-IO (ESMO 2021 #47LBA). The Net Treatment Benefit (NTB) is an original method combining efficacy and safety endpoints to test the overall improvement in health outcome between 2 treatments (Buyse M. Stat Med 2010). NTB was assessed in the overall population (N=219) from whom OS improvement of OSE2101 (HR 0.86, p=0.35) was lower than in PoI. Methods: NTB was tested by comparing prioritized outcomes using Generalized Paired Wise Comparisons (GPC). The prioritized outcomes were OS, then time to worsening ECOG (threshold=2 months) followed by severe adverse events, progression free survival (shorter vs. longer than 2 months) and Quality of Life (threshold=5 points on Global Health Status of EORTC-QLQC30). Analysis was stratified using the 3 strata of the study (histology, best response to 1rst line, line of prior IO) and enrollment time (before vs during COVID-19). Sensitivity analyses used no stratification, different thresholds of clinical relevance and PoI. Results: In the primary analysis (1088 pairs), NTB was 19% and reached statistical significance in favor of OSE2101 (p=0.035). In unstratified analysis (11120 pairs), NTB was 11% (p=0.188). In the PoI (388 pairs), NTB was 22% (p stratified=0.074) and 28% (p=0.014) in unstratified analysis (3040 pairs). Although the primary analysis was statistically positive, results were not consistent in some sensitivity analyses due to the limited sample size and the impact of stratification factors. Conclusions: An overall improvement in health outcome was observed with OSE2101 in the overall population of advanced NSCLC after IO failure with a NTB of 19% over SoC. In PoI with IO secondary resistance after CT-IO, the NTB was 22%. Post-hoc analyses are ongoing intended to explain the variability of NTB and will be detailed. Clinical trial identification: EudraCT: 2015-003183-36;NCT02654587. Editorial acknowledgement: We thank Pierre Attali (Medical Expert, MD) for his support in the writing of the . Legal entity responsible for the study: Ose Immunotherapeutics. Funding: Ose Immunotherapeutics. Disclosure: M.E. Buyse: Financial Interests, Personal, Officer, Chief Scientific Officer: IDDI;Financial Interests, Personal, Invited Speaker, Board Member: CluePoints;Financial Interests, Personal, Stocks/Shares: IDDI, CluePoints. F. Montestruc: Financial Interests, Personal, Member of the Board of Directors, CEO of the Company: eXYSTAT SAS;Financial Interests, Institutional, Other, Statistician Consultant: AbbVie, Biocodex, Geneuro, Gensight, Guerbet, Imcheck, Ose Immunotherapeutics, Pfizer, Takeda;Non-Financial Interests, Personal, Other, Statistician Consultant and Training: Institut Pasteur. J. Chiem: Financial Interests, Personal, Full or part-time Employment: IDDI. V. Deltuvaite-Thomas: Financial Interests, Personal, Full or part-time Employment: IDDI. S. Salvaggio: Financial Interests, Personal, Full or part-time Employment, Working as a statistician: International Drug Development Institute. M.R. Garcia Campelo: Financial Interests, Personal, Advisory Role: Roche/Genentech, MSD Oncology, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, Janssen Oncology;Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, MSD Oncology, Sanofi/Aventis, Janssen Oncology, Amgen;Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche/Genentech, MSD Oncology, Pfizer. F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD;Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, Galecto and MS . S. Viteri Ramirez: Financial Interests, Personal, Advisory Board: Merck Healthcare KGAA Germany, Bristol Myers Squibb S.A. U, Puma Biotechnology;Financial Interests, Personal, Invited Speaker: Takeda Farmaceutica España SA, MSD de España SA, AstraZeneca Farmaceutica Spain, Roche Farma SA;Financial Interests, Personal, Expert Testimony: Reddy Pharma Iberia SAU. W. Schuette: Financial Interests, Personal, Other, Honoraria: Roche, MSD, Novartis;Financial Interests, Personal, Advisory Role: Roche, MSD, Novartis. A. Zer: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Takeda, Pfizer, Novartis;Financial Interests, Personal, Advisory Board: AstraZeneca, Steba, Oncohost;Financial Interests, Personal, Stocks/Shares: Nixio;Financial Interests, Institutional, Research Grant: BMS. S. Comis: Financial Interests, Personal, Full or part-time Employment: Ose Immunotherapeutics. B. Vasseur: Financial Interests, Personal, Full or part-time Employment: Ose Immunotherapeutics;Financial Interests, Personal, Other, Actions: Ose Immunotherapeutics. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Seattle Genetics, Pfizer, Takeda, Regeneron, MSD, Bristol Myers-Squibb, PharmaMar, Bayer;Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Foundation Medicine;Financial Interests, Personal, Expert Testimony: Novartis;Financial Interests, Personal and Institutional, Invited Speaker: Roche, AstraZeneca, MSD, Amgen, Celon Pharma, Pfizer, Novartis, Brsitol Myers-Squibb, Eli Lilly, Loxo;Financial Interests, Invited Speaker: BeiGene, Ardigen, Ose Immunotherapeutics;Financial Interests, Personal and Institutional, Other, Subinvestigator and ad hoc Consultant: PDC* line Pharma;Non-Financial Interests, Institutional, Product Samples: Novartis, Pfizer, AstraZeneca, Roche;Other, Travel: Roche, Bristol Myers-Squibb, AstraZeneca. G. Giaccone: Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Institutional, Research Grant: Karyopharm. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, EISAI, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Medical Trends, Merck Sharp & Dohme, Pfizer, Puma, Sanofi, Takeda, Merck Serono, Peptomyc, Regeneron, Syneos Health, F. Hoffmann-La Roche;Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Springer, Touch Medical, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono;Financial Interests, Personal, Invited Speaker, Independent member: Grifols;Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc, Exelixis Inc, Merck KGAA, Janssen Cilag International NV, GlaxoSmithKline Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Farmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc, Bristol-Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc;Non-Financial Interests, Leadership Role, President Elect (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica);Non-Financial Interests, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO;Non-Financial Interests, Leadership Role, Member of Board of Directors and the Executive Committee (2017-Sept 2021): IASLC (International Association for the Study of Lung Cancer);Non-Fina cial Interests, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). All other authors have declared no conflicts of interest.